Structural Studies to understand molecular mechanisms of regulation of transcription initiation by small RNAs

Applications are invited for a Ph.D studentship to start in Sep 2017 in Dr. Vidya Darbari’s group in Queen Mary University of London to investigate transcription regulation by regulatory RNAs using structural biology techniques.

Transcription regulation allows orchestration of genetic activity to globally control cellular responses to special circumstances such as nutrient limitation, virulence etc. RNA polymerase is the central enzyme with a core structure that is conserved across all domains in life. It associates with specific transcription factors or Sigma factors to specifically recognize promoter sequences of DNA molecules to bring about RNA synthesis. Recently, the role of regulatory RNAs in controlling transcription is gaining significance. Many of the regulatory RNAs interact directly with mRNAs to regulate transcription. However some of the regulatory RNAs directly interact with the polymerase holoenzyme machinery to influence transcription. One such global regulatory RNA is the 6S RNA that has been widely studied biochemically. 6S RNA is a non-coding RNA that influences adaptation of the bacteria during stationary phase, sporulation, light adaptation or intracellular bacterial survival. It plays the role of a riboregulator by directly and indirectly affecting transcription of various genes during stress response. Structural and functional studies to understand the molecular recognition of small RNA by a DNA-dependent RNA polymerase, its binding specificity to the sigma factor or polymerase or both, RNA dependent RNA transcription by the polymerase and its release from the holoenzyme are required to understand this level of transcription regulation in great molecular detail. This can provide future directions in RNA-based antimicrobials.

Techniques and Training: Students will gain wide experience in biochemical and biophysical techniques to characterise protein-nucleic acid interactions and structural biology techniques including X-ray crystallography or Electron microscopy to determine various complex structures. The research group has a strong expertise with various structural techniques employed to study bacterial transcription initiation complexes with the variant sigma factor and have strong collaborative links with groups in Imperial College for RNA related complementary techniques. The training will also include the development of skills essential for career progression, including management of research projects, presentation and writing skills.

Environment: Queen Mary University of London is a member of the Russell group and is one of the leading research-focused institutions in the UK. All PhD students and post-doctoral researchers are part of the QMUL Doctoral College, which provides support with high-quality training and career development activities.

For informal enquires please contact Dr. Darbari and include your CV, a covering letter explaining eligibility and interest in the project and the contact details of two academic referees.